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Updated: Aug 18, 2026
Assessing Functional Performance in the Mdx Mouse Model
Published on: March 27, 2014
Impaired voluntary running capacity of creatine kinase-deficient mice
Iman Momken1, Patrick Lechêne, Nathalie Koulmann
1Cellular and Molecular Cardiology, INSERM U-446, Pharmacy Faculty, Paris South University, Châtenay-Malabry, France.
Abstract:
The creatine kinase system (CK) is important for energy delivery in skeletal and cardiac muscles. The two main isoforms of this enzyme, cytosolic MM-CK and mitochondrial mi-CK, are expressed in a developmental and muscle-type specific manner. Mice deficient in one or both of these isoforms are viable and fertile but exhibit profound functional, metabolic and structural muscle remodelling that primarily affects fast skeletal muscles, which show an increased contribution of oxidative metabolism to contractile function. However, the consequences of these alterations in terms of physical capabilities have not yet been characterized. Consequently, we compared the voluntary exercise capacity of 9-month-old male wild-type (WT), M-CK knockout (M-CK(-/-)), and M-CK and mi-CK double knockout (CK(-/-)) mice, using cages equipped with running wheels. Exercise performance, calculated by total distance covered and by work done during the training period, was more than 10-fold lower in CK(-/-) mice than controls, with M-CK(-/-) mice exhibiting intermediate performance. Similarly, the mean distance run per activation was lower in M-CK(-/-) and even lower in CK(-/-) mice. However, the maximal running speed (V(max)) was lower only for CK(-/-) mice. This was accompanied by severe skeletal muscle mass decrease in CK(-/-) mice, with signs of histological damage that included enlarged interstitial areas, aggregations of mononuclear cells in the interstitium, heterogeneity of myofibre size and the presence of very small fibres. No overt sign of cardiac dysfunction was observed by magnetic resonance imaging during dobutamine stimulation. These results show that metabolic failure induced by CK deficiency profoundly affects the ability of mice to engage in chronic bouts of endurance running exercise and that this decrease in performance is also associated with muscle wasting.
Insights
Mice lacking creatine kinase (CK) enzymes show significantly reduced exercise capacity and muscle mass. This highlights the critical role of CK in energy metabolism for sustained physical activity and muscle health.
Area of Science:
- Muscle physiology
- Energy metabolism
- Biochemistry
Background:
- The creatine kinase (CK) system is crucial for energy buffering and delivery in muscle tissues.
- Specific isoforms, MM-CK and mi-CK, are vital for skeletal and cardiac muscle function, with distinct expression patterns.
- Mice lacking CK isoforms undergo muscle remodeling, but their physical performance consequences remain uncharacterized.
Purpose of the Study:
- To investigate the impact of creatine kinase deficiency on voluntary exercise capacity and physical performance in mice.
- To characterize the functional and structural consequences of combined M-CK and mi-CK deficiency in skeletal muscle.
Main Methods:
- Comparison of voluntary exercise capacity using running wheels in wild-type, M-CK knockout, and double M-CK/mi-CK knockout mice.
- Assessment of exercise performance metrics including total distance, work done, and maximal running speed.
- Histological analysis of skeletal muscle and cardiac function evaluation via MRI during dobutamine stimulation.
Main Results:
- Double CK knockout mice exhibited over a 10-fold reduction in exercise performance compared to controls.
- M-CK knockout mice showed intermediate performance, while maximal running speed was only reduced in double knockouts.
- CK deficiency led to severe skeletal muscle mass reduction, histological damage, and interstitial changes, without apparent cardiac dysfunction.
Conclusions:
- Metabolic failure due to creatine kinase deficiency severely impairs endurance running capacity in mice.
- Decreased physical performance in CK-deficient mice is associated with significant muscle wasting and structural damage.
- The creatine kinase system is essential for maintaining muscle function and integrity during prolonged physical exertion.
